Vol. 305, Issue 2, 719-724, May 2003

Norepinephrine Evoked by Potassium Depolarization Increases Interstitial Adenosine Concentration via Activation of ecto-5'-Nucleotidase in Rat Hearts

Toshio Obata, Hidetoshi Yonemochi and Makoto Arita

Departments of Pharmacology and Therapeutics (T.O.) and Cardiovascular Science (H.Y.), Oita Medical University, Oita, Japan; and Yufuin-Kohoseinenkin Hospital (M.A.), Oita, Japan

We examined whether the increase of the extracellular potassium ion concentration, [K⁺]_o, can increase the production of interstitial adenosine in the ventricular myocardium, with the use of microdialysis techniques in in situ rat hearts. A microdialysis probe was implanted in the left ventricular myocardium of anesthetized rat hearts, and the tissue in the vicinity of the dialysis was perfused with Tyrode's solution containing AMP through the dialysis probe at a rate of 1.0 µl/min to assess the activity of ecto-5'-nucleotidase. When the K⁺ concentration of the perfusate ([K⁺]_o) was increased stepwise from 5.4 mM (control) to up to 140.4 mM, the level of dialysate adenosine significantly increased, in a [K⁺]_o-dependent manner. The presence of CsCl or BaCl₂ (20 mM), which markedly depolarized the resting potential, significantly increased the level of adenosine in the dialysate. Equivalent increases in the osmotic concentration of the perfusate, made by adding sucrose (270 mM), did not change the dialysate adenosine concentration. Introduction of high [K⁺]_o (140.4 mM) significantly increased the level of norepinephrine (NE) in the dialysate, and this increase was abolished in the reserpinized rats hearts. In the presence of an antagonist of ₁-adrenoceptor (prazosin, 50 µM) or protein kinase C (PKC) (chelerythrine, 10 µM) and in reserpinized rats, an introduction of high [K⁺]_o failed to increase the AMP-primed dialysate adenosine concentration. We conclude that high [K⁺]_o-induced NE release from sympathetic nerve terminals increases adenosine by stimulating the PKC-ecto-5'-nucleotidase cascade through ₁-adrenoceptors.